Assuntos
Adjuvantes Imunológicos/imunologia , Benzofuranos/imunologia , Encefalomielite Equina/microbiologia , Encefalomielite Equina Venezuelana/microbiologia , Fluorenos/imunologia , Tilorona/imunologia , Vacinas Atenuadas/imunologia , Animais , Anticorpos Antivirais/análise , Formação de Anticorpos , Feminino , Formaldeído , Macaca mulatta , Masculino , CamundongosRESUMO
A new, formalin-inactivated vaccine for Venezuelan equine encephalitis (VEE) virus (C-84), prepared from an attenuated vaccine strain of virus (TC-83), was tested in humans. Only occasional, mild, local and systemic reactions were noted in 28 volunteers; no meaningful changes in clinical laboratory values occurred. The vaccine augmented preexisting titers of serum neutralizing antibody to VEE virus in seropositive recipients of TC-83 vaccine, and it induced high titers of neutralizing antibody in nonimmune subjects after one primary and two booster vaccinations. Circulating antibody persisted for at least 14 months in these persons. The neutralizing antibody produced after one dose of C-84 vaccine in immune subjects and after booster doses in nonimmune subjects had broad cross-reactivity within the VEE virus complex. The C-84 vaccine induced a VEE virus-specific lymphocyte transformation response. The vaccine was safe, and immunologic results showed it to be highly antigenic in healthy immune and nomimmune adults.
Assuntos
Anticorpos Antivirais/biossíntese , Vírus da Encefalite Equina Venezuelana/imunologia , Vacinas Virais/uso terapêutico , Adolescente , Adulto , Animais , Vírus da Encefalite Equina do Leste/imunologia , Vírus da Encefalite Equina do Oeste/imunologia , Feminino , Humanos , Injeções Intradérmicas , Injeções Subcutâneas , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Testes Cutâneos , Vacinas Virais/efeitos adversosRESUMO
Polyriboinosinic.polyribocytidylic acid [poly(I).poly(C)] stabilized with poly-l-lysine and carboxymethylcellulose [poly(ICLC)] has been previously shown to be a compound with marked adjuvant activity when given in high doses with inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccine. This study investigated the effects of much lower doses of poly(ICLC) on the magnitude and kinetics of the primary and secondary humoral antibody responses of rhesus monkeys to inactivated VEE virus vaccine. Monkeys given a single injection of vaccine developed very low neutralizing antibody titers, whereas those given adjuvant plus vaccine had 30- to 100-fold-higher titers which remained elevated for longer than 6 months. Low doses of poly(ICLC) given with VEE virus vaccine resulted in a profound but transient increase in priming of secondary antibody responses to the antigen. In contrast, the administration of poly-l-lysine and carboxymethylcellulose alone without the poly(I).poly(C) component of the complex had no adjuvant effect on antibody responses of monkeys to VEE virus vaccine. The temporal development of antibody by class (immunoglobulin M-immunoglobulin G) in monkeys given two injections of adjuvant-vaccine was not different from that with vaccine alone. Serial hematological and clinical chemistry determinations on monkeys given single or multiple doses of poly(ICLC) with vaccine were not different from values in monkeys given vaccine alone.
Assuntos
Adjuvantes Imunológicos , Vírus da Encefalite Equina Venezuelana/imunologia , Poli I-C/imunologia , Animais , Anticorpos Antivirais/biossíntese , Formação de Anticorpos , Haplorrinos , Interferons/biossíntese , Macaca mulatta , Vacinas ViraisRESUMO
Primary chicken embryo cell cultures were evaluated a s an alternate cell system for the production of attenuated Venezuelan equine encephalomyelitis (TC-83 strain) vaccine. The TC-83 strain virus was shown to remain stable during 10 serial passages in chicken embryo cell culture with regard to plaque size and morphology, virus yield, potency, and virulence for mice and hamsters.
Assuntos
Vírus da Encefalite Equina Venezuelana/imunologia , Vacinas Atenuadas , Vacinas Virais , Animais , Embrião de Galinha , Cricetinae , Técnicas de Cultura , Vírus da Encefalite Equina Venezuelana/crescimento & desenvolvimento , Vírus da Encefalite Equina Venezuelana/patogenicidade , Estudos de Avaliação como Assunto , Coração Fetal , Cobaias , Imunoquímica , Camundongos , VirulênciaRESUMO
Formalin-inactivated Venezuelan equine encephalomyelitis vaccine was prepared from virus propagated in rolling-bottle cultures of chicken embryo cells. The attenuated, TC-83 strain of virus was propagated in these cultures with a maintenance medium consisting of serum-free medium 199 containing 0.25% human serum albumin and antibiotics. By adjustment of maintenance medium volume (100 to 300 ml) and multiplicity of inoculum (0.04 to 0.00004), high-titered yields of virus were obtained with minimal cell destruction at convenient harvest times, viz, 18 to 24 h postinoculation. Inactivation of virus at 37 C was complete between 8 to 10 h with 0.05% Formalin and within 6 to 8 h with 0.1% Formalin. Antigen extinction potency tests in mice indicated that potent vaccines could be produced at both Formalin concentrations and, furthermore, that potency was not adversely affected by inactivation periods of up to 96 h.
Assuntos
Vírus da Encefalite Equina Venezuelana/imunologia , Vacinas Virais/farmacologia , Animais , Células Cultivadas , Embrião de Galinha , Técnicas de Cultura , Vírus da Encefalite Equina Venezuelana/efeitos dos fármacos , Vírus da Encefalite Equina Venezuelana/crescimento & desenvolvimento , Vírus da Encefalite Equina Venezuelana/patogenicidade , Estudos de Avaliação como Assunto , Formaldeído/farmacologia , Dose Letal Mediana , CamundongosRESUMO
Formalin-inactivated Venezuelan equine encephalomyelitis vaccine was prepared from virus grown in rolling-bottle cultures of chicken embryo cells. Trinidad strain virus was propagated in these cultures with a maintenance medium consisting of serum-free medium 199 containing 0.25% human serum albumin (USP) and antibiotics. Manipulation of multiplicity of inoculum (0.06 to 0.00006) and maintenance medium volume (100 to 300 ml) resulted in high-titered virus yields and only moderate cell destruction when fluids from infected cultures were harvested at 18 to 24 hr. The virus was inactivated at 37 C by 0.05% Formalin within 8 to 10 hr and with 0.1% Formalin within 6 to 8 hr. Single dose, antigen extinction tests in mice performed with 30 small-scale vaccine lots showed excellent potency at either Formalin concentration with inactivation periods ranging from 24 to 96 hr.
Assuntos
Vírus da Encefalite Equina Venezuelana/imunologia , Vacinas Virais , Cultura de Vírus , Animais , Embrião de Galinha , Meios de Cultura , Técnicas de Cultura , Vírus da Encefalite Equina Venezuelana/efeitos dos fármacos , Vírus da Encefalite Equina Venezuelana/crescimento & desenvolvimento , Formaldeído/farmacologia , Camundongos , Vacinas Virais/farmacologia , Vacinas Virais/normasRESUMO
The rapid onset and persistence of homologous and heterologous protection induced by attenuated Venezuelan equine encephalomyelitis (VEE) vaccine (TC-83) were studied in the hamster, by using challenge response as the index of protection. At 8 hr postvaccination with 10(3) median immunizing doses of TC-83 vaccine, 15 to 20% of animals were protected against challenge with VEE virus as well as Eastern and Western equine encephalomyelitis viruses. The percentage of protection increased with time postvaccination until 80 to 90% homologous and heterologous protection was achieved by 18 hr postvaccination. Temporal studies indicated that early protection (days 1 to 6) correlated with vaccine viremia, and that the percentage of protection against heterologous challenge decreased with the cessation of viremia. Data are presented to indicate that the early protection phenomenon is one of interference, since little or no replication of a challenge virus occurred when it was administered during the vaccine viremia stage.